tbuckley/cabot-search huggingface dataset:
Liraglutide treatment attenuates dysfunction-related changes in the cardiac and cerebral microvasculature in streptozotocin-induced diabetic rats
Authors: A Korn, U Baylan, RW Emmens, CG Schalkwijk, HWM Niessen, PAJ Krijnen, S Simsek
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Background Diabetes mellitus (DM) induces cardiac and cerebral microvascular dysfunction via increased glycation, oxidative stress and endothelial activation. Liraglutide, a glucagon-like peptide-1 receptor analogue, inhibited the reactive oxygen species producing enzyme NOX2 and adhesion molecules in isolated endothelial cells. Here we have studied how Liraglutide affects advanced glycation, NOX expression and inflammatory status of the cardiac and cerebral microvasculature in vivo in diabetic rats. Methods DM was induced in Sprague Dawley rats (n=15) via intraperitoneal streptozotocin (STZ) injection (60 mg/kg body weight). 10 control rats remained non-diabetic. From day 9 post-STZ injection, Liraglutide (200 µg/kg bodyweight; n=7) or vehicle (n=8) was injected subcutaneously daily until termination on day 29. The advanced glycation end-product N-ε-(carboxymethyl)lysine (CML), NOX2, NOX4, ICAM-1 and VCAM-1 were subsequently analysed using immunohistochemistry and quantified to compare Liraglutide treatment to placebo. Results DM increased CML, NOX2, ICAM-1 and VCAM-1 in the intramyocardial vasculature, although not significant for NOX2. NOX4 was not significantly increased in the ventricles and absent in the atria. In the cerebral vasculature, CML, NOX2 and NOX4 were significantly increased, but not ICAM-1 and VCAM-1. Liraglutide significantly reduced the DM-associated CML accumulation and expression of NOX2, ICAM-1 and VCAM-1 in the intramyocardial, and CML, NOX2 and NOX4 in the cerebral vasculature. Liraglutide had these effects without changing blood glucose levels or body weight. Conclusions Our study implies that Liraglutide protects the cardiac and cerebral microvasculature against diabetes-induced dysfunction, independent of a blood glucose lowering effect in a type 1 diabetes rat model.
The surgical learning curve for positive surgical margins after robot-assisted radical prostatectomy: Results from a multi-institutional collaboration
Authors: C.A. Bravi, P. Piazza, E. Mazzone, L. Sarchi, S. Scarcella, S. Puliatti, S. Knipper, P. Dell'Oglio, A. Galfano, N. Suardi, C. Terrone, R. Autorino, U. Falagario, G. Carrieri, A. Galosi, R. Schiavina, R. De Groote, M. Moschovas, V. Patel, A. Vickers, A. Briganti, F. Montorsi, A. Mottrie
Journal: European Urology (2022)
The use of medical cannabis concomitantly with immune-check point inhibitors (ICI) in non-small cell lung cancer (NSCLC): A sigh of relief?
Authors: Barliz Waissengrin, Yasmin Leshem, Ofer Merimsky, Ido Wolf
Journal: Journal of Clinical Oncology (2022)

e21097 Background: In recent years, the use of medical cannabis rapidly increased among cancer patients in Israel. Yet, cannabinoid receptors are abundantly expressed on immune cells and modulate their activity. It is abundantly being use by metastatic NSCLC patients, shortly following diagnosis and is taken in parallel to first line treatment with ICI. Recent studies suggested that the use of cannabis may reduce the efficacy of ICI. However, these studies were biased by the heterogeneity of patients and the increased use of cannabis specifically in highly symptomatic patients with high disease burden. Methods: We first tested the interaction anti-PD-1 antibody and Δ−9-tetrahydrocannabinol (THC) in a preclinical model consisting of CT26 tumor-bearing mice, and examined the effects on tumor size, T-cell infiltrates, and mice survival. Mice were euthanized when tumor volume reached above 700 mm 3 . Next, we conducted a retrospective study of NSCLC patients, treated at a tertiary center, and included all consecutive patients treated with a single agent pembrolizumab as a first line treatment for advanced disease and evaluated clinical outcome and response to treatment. Results: Studies using the CT26 mice cancer model, indicated a potential beneficial effect for the combination an anti-PD-1 antibody and THC with a median overall survival (OS) of the mice receiving no treatment, THC, anti-PD-1 antibody or their combination being 21 days, 24, 31 days and 54 days, respectively (p &lt; 0.05). Data of 201 NSCLC cancer patients who received first-line single agent pembrolizumab for metastatic disease, 102 (50.7%) patients received cannabis and 99 (49.3%) were cannabis naïve was analyzed. Their median age was 68 for the cannabis treated group and 74 for the cannabis naïve (p = 0.003), 34 (34.3%) in the cannabis treated group and 62 (60.8%) for the cannabis naïve were women (p = 0.002). Similar distribution of histology, smoking status and PDL1 expression was noted between the groups. The efficacy of pembrolizumab, as determined by time to progression (TTP) was similar for cannabis-naïve and cannabis-treated patients (6.1 vs. 4.8 months, respectively, p = 0.386), while OS was higher, though not statistically significant, in the cannabis-naïve group (54 vs. 23.3 months, respectively p = 0.08). Conclusions: Both preclinical and clinical data suggest no deleterious effect of cannabis on the activity of pembrolizumab as first line monotherapy for advanced NSCLC. The differences in OS can be most likely by attributed to higher disease burden and more symptomatic disease in the cannabis-treated group. While additional validation is required, these data provide somewhat reassuring data regarding the absence of a deleterious effect of cannabis in this clinical setting.
Intratumoral CD8+ t cell as a potential positive predictor for treatment of chemo-immunotherapy in PD-L1 negative advanced gastric cancer patients.
Authors: Gangling Tong, Meiqin Zhu, Yaoxu Chen, Shubo Wang, Boran Cheng, Shubin Wang, Wangjun Liao
Journal: Journal of Clinical Oncology (2022)

e16029 Background: It was demonstrated that CPS PDL1 positive patients of advanced gastric cancer (GC) could benefit from specific immune checkpoint inhibitors (ICI) for first-line, and second-line or subsequent therapy. However, whether the application of ICI could lead to better clinical outcome in advanced GC patients who were negative for PDL1 remains further explore. Some studies showed that patients with specific tumor immune microenvironment (TME) are more sensitive to immunotherapy. Therefore, TME may be a potential positive predictor for PDL1 negative patients treated with immunotherapy. Methods: We retrospectively enrolled 26 advanced GC patients who were treated by chemoimmunotherapy in Shenzhen Hospital of Peking University and evaluated for clinical characteristics. Peritumoral and intratumoral Tumour-infiltrating lymphocytes (TIL) were detected by mIHC (multiplex immunofluorescence) among these patients. The correlation between PFS and clinical characteristics including TIL was analyzed by univariate survival analysis and multivariate Cox proportional hazards analysis. Results: In 26 patients, 5 patients (19.2%) experienced complete response (CR), 9 patients (34.6%) experienced partial response (PR), while 7 patients (26.9%) experienced stable disease (SD). Compared with non-responders, higher intratumoral infiltrating CD8+ T cells instead of other subtypes were detected in CPS PDL1 negative Patients who respond to chemoimmunotherapy. Further analysis revealed that CD8+ TIL was a predictive biomarker for PFS to chemo-immunotherapy in CPS PDL1 negative patients. Conclusions: For CPS PDL1 negative advanced GC patients, intratumoral CD8+ TIL may be a potential positive predictor for treatment of chemo-immunotherapy.
Robotic partial nephrectomies with selective/superselective clamping of renal artery branch by using indocyanine green (ICG)
Authors: Y. Kordan, E. Köseoğlu, A.F. Sarıkaya, K. Tarım, M. Kılıç, A. Özkan, M.C. Kiremit, A.E. Canda, M.D. Balbay, T. Esen
Journal: European Urology (2022)
Contact x-ray brachytherapy (Papillon) in addition to chemoradiotherapy to improve organ preservation in early cT2-T3 rectal adenocarcinoma: The 3-year results of OPERA randomized trial (NCT02505750).
Authors: Jean-Pierre Gerard, Nicolas N. Barbet, Tanguy Pacé-Loscos, Nicolas Magné, Jessica Serrand, Laurent Mineur, Melanie Deberne, Thomas Zilli, Amandeep Singh Dhadda, Arthur Sun Myint
Journal: Journal of Clinical Oncology (2022)

3512 Background: The OPERA trial was testing the hypothesis that Contact x-ray brachytherapy (CXB) 50 kV boost will increase the rectal preservation rate in early T2-T3ab rectal adenocarcinoma. We present the 3 years clinical results. Methods: Inclusion criteria were: Age &gt; 18 years, PS: 0-1, adenocarcinoma, distal - middle rectum, cT2-T3ab cN0-N1 &lt; 8mm staged using MRI, M0. Stratification: T &lt; vs ≥ 3 cm diameter. Control arm (A) was chemoradiotherapy (CRT) 45Gy/ 5 weeks with concurrent chemotherapy (Capecitabine 825 mg / m 2 ) and external beam radiotherapy boost (9Gy/ 5 fr/ 1 week). Experimental arm used the same CRT (Cape 45) but the boost used CXB (90 Gy/ 3 fr/ 4 weeks). CXB was given first (B1) for tumor &lt; 3 cm and after cap 45 (B2) for tumor ≥ 3 cm. Response assessment was made at week 14 after treatment start using palpation, endoscopy and MRI. A new assessment could be made at week 20 and 24 with a second MRI.TME was recommended in case of Partial response, Watch&amp; Wait in case of clinical complete response (cCR). Bowel function measurement used LARS score. Main end- point was: Rate of organ preservation at 3 years. The hypothesis (in 2014) was 20% arm A vs 40% arm B (HR:0.53). Results: Between 5-2015 and 6-2020, 144 patients were included (France 96, UK 44, Switzerland 4). The analysis was made in 01-2022 with a median Follow-up time of 34 months. Treatment compliance was good in ≥ 90% of patients. Table gives main patients characteristics and clinical outcome. At three years the OP rate (Kaplan Meier estimate) was respectively arm A vs B: 60% vs 81% (HR 0.34 [95% CI 0.19 – 0.73]; p= 0.005). At three years OP for group A1 and B1 were: 65% vs 97% (HR 0.081 [95% CI 0.01-0.64]; p= 0.02). Conclusions: A CXB boost, when combined with chemoradiotherapy, increases the rate of organ preservation in early rectal adenocarcinoma. Starting with CXB in T &lt; 3 cm appears as an attractive option. A B A1 (T &lt; 3cm) B1 (T &lt; 3cm) N° patient 71 73 30 32 Median age 68 69 69 70 Gender M/F 45/26 43/30 18/12 18/14 T2/T3 45/26 47/26 25/5 29/3 Distal/middle 53/18 53/20 21/9 27/5 cCR (W 14-24) 61% 90% p &lt; 0.001 70% 94% p = 0.027 TME 26 12 8 1 Death 2 2 1 0 LARS &lt; 30 80% 83% 87% 86%.
Caloric restriction ketogenic diets (KR) in relation to radiotherapy responses in lung cancer xenografts
Authors: Jiahua Lyu, Ling Xiao, Yudi Liu, Yuan Wang, Rongke Zhang, Taiyu Chen, Hangyue Zhang, Chunhan Tang, Shiyi Pan, Xinyu Nie, Min Zhang, Tao Li
Journal: Journal of Clinical Oncology (2022)

e20528 Background: Dietary interventions can change metabolite levels in the tumour microenvironment, which might then affect cancer cell metabolism to alter tumour growth. Caloric restriction (CR) and ketogenic diet (KD) are often thought to limit tumour progression. The current study tests the hypothesis that caloric restriction ketogenic diets (KR) enhance radiotherapy responses in lung cancer xenografts. Methods: Mice bearing Lewis Lung Carcinoma xenografts were randomly divided into ad libitum diet group (AL), radiation group (RT), KR diet group (KR), or KR + RT group (KT). Mice in KR and KT group were fed a KR (KetoCal 4:1 fats: proteins+carbohydrates;70% of total energy). Mice in RT and KT group were treated with radiation (4Gy*3f). Mice weights, tumor size, blood ketone levels and survival were monitored. Results: Blood ketone levels were significantly higher for the mice consuming a KR diet compared to standard diet (3.2 mmol/L vs 0.8 mmol/L at week 3, P &lt; .001). Some mice with KR diet lost a significant amount of weight (10%～15% of starting weight) by the end of the treatment.The KR diets combined with radiation resulted in slower tumor growth in Lewis Lung Carcinoma xenografts and longer survival time (P &lt; 0.05), relative to radiation alone. The KR diet also slowed tumor growth and prolonged survival (P &lt; 0.05), relative to control. Hematological and pathological examinations indicated that the KR diet was safe and well tolerated, and no significant cardiac, hepatic and renal toxicity was observed. Conclusions: These results showed that a KR diet enhanced radiotherapy responses in lung cancer xenografts. Further studies are needed to address the mechanism of this diet intervention.
Neighborhood socioeconomic disadvantage, tobacco use, and cessation indicators among adults with cancer in the United States: Results from 10 ECOG-ACRIN trials.
Authors: Angela Wangari Walter, Ju-Whei Lee, Ilana F. Gareen, Sheetal Mehta Kircher, Benjamin A. Herman, Joanna M. Streck, Shaji Kumar, Ingrid A. Mayer, Nabil F. Saba, Joel W. Neal, Michael B. Atkins, F. Stephen Hodi, Christos Kyriakopoulos, Clare Tempany, Tait D. Shanafelt, Lynne I. Wagner, Stephanie R. Land, Jamie S. Ostroff, Elyse R. Park
Journal: Journal of Clinical Oncology (2022)

6514 Background: Tobacco use is a modifiable risk factor for adverse outcomes among patients diagnosed with cancer. Despite ASCO’s recommendation for assessment and treatment of tobacco use, integration into cancer care is suboptimal. Socioeconomic contexts influence access and utilization of tobacco treatment, but little is known about the relationship between neighborhood socioeconomic disadvantage (NSD) and tobacco assessment, assistance, and cessation among cancer patients enrolled in clinical trials. Methods: The NCI Cancer Patient Tobacco Use Questionnaire (C-TUQ) was centrally administered to participants enrolled in 10 ECOG ACRIN clinical trials (9 therapeutic, 1 imaging). We examined associations of NSD with patient-reported rates of receiving brief tobacco cessation support (i.e., Ask, Assist (counseling)) and cessation (past 30d quit attempts and duration). NSD was measured using the national Area Deprivation Index (ADI) based on participant’s zip code. Associations between ADI (low, intermediate, and high) and tobacco variables were evaluated using logistic regression and ANOVA. Results: 740 patients, completing the C-TUQ between June 2017-October 2021, can be classified as 402 (54%) never smokers, 81 (11%) current smokers, and 257 (35%) former smokers. Patients were 70% male; 94% white; 3% Hispanic; mean age 58.8 (SD 9.0). Cancer diagnoses were 36% leukemia; 19% lymphoma, 18% prostate, 11% breast; 9% melanoma, 7% myeloma, and 0.5% head and neck. Patients were categorized into high (33%), intermediate (34%) and low (33%) disadvantaged neighborhoods. Patients in high (vs. low) disadvantaged neighborhoods were more likely to report being asked about smoking (OR = 3.90; 95% CI (confidence interval), 1.61 to 9.46; p = 0.0062) but less likely to report receiving counseling to help quit smoking (OR = 0.20; 95% CI, 0.06 to 0.73; p = 0.0234). Patients from high disadvantaged neighborhoods had the shortest quit duration, followed by patients from intermediate and low disadvantaged neighborhoods (mean = 145.78, 187.66, and 210.98 months, respectively, p = 0.0372). Conclusions: Greater socioeconomic neighborhood disadvantage was associated with increased assessment of tobacco use but decreased tobacco treatment referral, and the shortest quit duration. More research is needed to promote increased referral to tobacco treatment for individuals with cancer from disadvantaged neighborhoods to promote and sustain cessation.
Conductive Hydrogel Conduits with Growth Factor Gradients for Peripheral Nerve Repair in Diabetics with Non‐Suture Tape
Authors: Yuting Cai, Qun Huang, Penghui Wang, Kaichuang Ye, Zhen Zhao, Haomin Chen, Zhenjing Liu, Hongwei Liu, Hoilun Wong, Mohsen Tamtaji, Kenan Zhang, Feng Xu, Guorui Jin, Lun Zeng, Jianbo Xie, Yucong Du, Zhigang Hu, Dazhi Sun, Jinbao Qin, Xinwu Lu, Zhengtang Luo
Journal: Advanced Healthcare Materials (2022)

Abstract Diabetic patients suffer from peripheral nerve injury with slow and incomplete regeneration owing to hyperglycemia and microvascular complications. This study develops a graphene‐based nerve guidance conduit by incorporating natural double network hydrogel and a neurotrophic concentration gradient with non‐invasive treatment for diabetics. GelMA/silk fibroin double network hydrogel plays quadruple roles for rapid setting/curing, suitable mechanical supporting, good biocompatibility, and sustainable growth factor delivery. Meanwhile, graphene mesh can improve the toughness of conduit and enhance conductivity of conduit for regeneration. Here, novel silk tapes show quick and tough adhesion of wet tissue by dual mechanism to replace suture step. The in vivo results demonstrate that gradient concentration of netrin‐1 in conduit have better performance than uniform concentration caused by chemotaxis phenomenon for axon extension, remyelination, and angiogenesis. Altogether, GelMA/silk graphene conduit with gradient netrin‐1 and dry double‐sided adhesive tape can significantly promote repairing of peripheral nerve injury and inhibit the atrophy of muscles for diabetics.
Diagnostic performance of micro-ultrasound guided reclassification biopsies in patients under active surveillance for prostate cancer
Authors: D. Maffei, P.P. Avolio, C. Saitta, M. Paciotti, V. Fasulo, E. Beatrici, C. Giuseppe, M. Lazzeri, A.R. Saita, R. Hurle, G.F. Guazzoni, P. Casale, N.M. Buffi, G. Lughezzani
Journal: European Urology (2022)
Gut microbiota differs between treatment outcomes early after fecal microbiota transplantation against recurrent <i>Clostridioides difficile</i> infection
Authors: Shaodong Wei, Martin Iain Bahl, Simon Mark Dahl Baunwall, Jens Frederik Dahlerup, Christian Lodberg Hvas, Tine Rask Licht
Journal: Gut Microbes (2022)

AbstarctIn fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (CDI), clinical outcomes are usually determined after 8 weeks. We hypothesized that the intestinal microbiota changes earlier than this timepoint, and analyzed fecal samples obtained 1 week after treatment from 64 patients diagnosed with recurrent CDI and included in a randomized clinical trial, where the infection was treated with either vancomycin-preceded FMT (N = 24), vancomycin (N = 16) or fidaxomicin (N = 24). In comparison with non-responders, patients with sustained resolution after FMT had increased microbial alpha diversity, enrichment of Ruminococcaceae and Lachnospiraceae, depletion of Enterobacteriaceae, more pronounced donor microbiota engraftment, and resolution of gut microbiota dysbiosis. We found that a constructed index, based on markers for the identified genera Escherichia and Blautia, successfully predicted clinical outcomes at Week 8, which exemplifies a way to utilize clinically feasible methods to predict treatment failure. Microbiota changes were restricted to patients who received FMT rather than antibiotic monotherapy, indicating that FMT confers treatment response in a different way than antibiotics. We suggest that early identification of microbial community structures after FMT is of clinical value to predict response to the treatment.
Sutureless off-clamp robotic partial nephrectomy as a viable option to improve perioperative surgical outcomes: Single center analysis
Authors: A. Brassetti, U. Anceschi, A. Bove, M. Costantini, M.C. Ferriero, S. Guaglianone, R. Mastroianni, L. Misuraca, G. Tuderti, G. Simone
Journal: European Urology (2022)
FGFR testing from matched tissue and urine samples from pilot cohort the prospective Real World clinico-pathological register trial „BRIDGister
Authors: R. Wirtz, R. Watts, R. Kellner, R. Ortmann, T. Horns, D. Enderle, L. Meyer, M. Noerholm, M. Morken, E. Veltrup, R. Hake, S. Eidt, J. Roggisch, S. Koch, T.H. Ecke
Journal: European Urology (2022)
Evaluation of inpatient chemotherapy among patients with cancer.
Authors: Giulia Petrone, Nobel Chowdhury, Shivani Handa, Justine Anderson, Deukwoo Kwon, Aarti Sonia Bhardwaj, Priya Jain, Cardinale B. Smith, Natalie S Berger
Journal: Journal of Clinical Oncology (2022)

6566 Background: Administration of inpatient chemotherapy (IC) is associated with more aggressive end of life care, reduced use of palliative care (PC) and decreased quality of life (QOL). This study aims to identify risk factors associated with overutilization of IC. Methods: We conducted a retrospective chart review of all admissions where IC was administered at an academic center between January 2016 and December 2017. Patients (pts) were stratified by solid tumors (ST) versus hematologic malignancies (HM) and urgency for IC was assessed. We evaluated other variables which can impact patient care such as length of stay (LOS), reason for admission and for IC. Descriptive statistics and odds ratios (OR) were estimated from logistic regression models with mixed-effect taking into account correlations from multiple admissions per patient. All tests were two-sided and statistical significance was considered when p&lt;.05. Results: We analyzed 880 admissions (17% ST). Table 1 summarizes outcomes. HM pts required frequent direct admission for IC compared to ST. ST pts (p&lt;.0001), pts &gt;65 years (p=0.004) and pts with KPS ≤50% (p&lt;.0001) were most likely admitted for cancer complications rather than for IC. LOS (&gt;7 days) was significantly longer in HM admissions (p=0.0001), among pts with stage 4 cancer (p=0.014) and KPS ≤50% (p=0.0001). ST (p=0.006) and pts with KPS ≤50% (p=0.0001) received IC for a non-urgent indication significantly more often than HM. In 20% of ST admissions, pts received IC because the admission coincided with a non-urgent planned cycle compared to 3% of HM. In the adjusted analysis, tumor type was the most important factor correlated with urgency of IC (OR 0.42, 95% CI: 0.25-0.72; p=0.001). ST pts (p=0.0001), older pts (p=0.004) and pts with KPS ≤50% (p=0.0001) were less likely to respond to chemotherapy. Only 15% of HM admissions and 46% of ST admissions had a PC consult. 60-day mortality was significantly higher in ST pts than HM (p=0.002). Conclusions: IC is associated with poorer outcomes for pts with advanced stage ST, pts with poor functional status and pts admitted for acute indications. Additionally, ST pts have a higher mortality after IC compared to HM. Utilization of IC should be standardized to account for different patient characteristics and to reduce the incidence of non-urgent administration. Based on this data, we created a standardized protocol to better assess the appropriateness of IC to improve patient care, QOL, and reduce chemotherapy and healthcare utilization at the end of life. [Table: see text]
Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization
Authors: Simon P. Jochems, Karin de Ruiter, Carla Solórzano, Astrid Voskamp, Elena Mitsi, Elissavet Nikolaou, Beatriz F. Carniel, Sherin Pojar, Esther L. German, Jesús Reiné, Alessandra Soares-Schanoski, Helen Hill, Rachel Robinson, Angela D. Hyder-Wright, Caroline M. Weight, Pascal F. Durrenberger, Robert S. Heyderman, Stephen B. Gordon, Hermelijn H. Smits, Britta C. Urban, Jamie Rylance, Andrea M. Collins, Mark D. Wilkie, Lepa Lazarova, Samuel C. Leong, Maria Yazdanbakhsh, Daniela M. Ferreira
Journal: Journal of Clinical Investigation (2022)

During the preparation of this manuscript, the labels for Figure 5, A and D, for Streptococcus pneumoniae (Spn) carriage -(Spn -) and carriage + (Spn + ) were inverted.